The invention relates to “active implantable medical devices” as defined by Directive 90/385/EEC of 20 Jun. 1990 of the Council of the European Communities, specifically implants for delivering therapies of stimulation of the vagus nerve, called VNS (Vagus Nerve Stimulation). The invention relates to the use of such therapies in patients at risk of heart failure.
Stimulation of the vagus nerve affects the cardiovascular functions by reducing the heart rate and myocardial contractility with decreased duration of diastole, which can help reduce the progression of cardiac remodeling that may lead to heart failure. Such VNS devices may include a lead, an electrode implanted on the vagus nerve, and a generator supplying VNS pulses on this electrode via the lead.
When the vagus nerve is stimulated in synchrony with the heartbeat, the device may include one or more cardiac leads. The cardiac leads may include, for example, one or more endocardial leads or one or more leads implanted in the coronary network for the collection of cardiac depolarization waves (electrogram EGM). In some devices the cardiac leads are also able to deliver myocardial stimulation pulses (stimulation of ventricular and/or atrial cavities), in addition to the VNS stimulation separately applied on the vagus nerve.
Other methods for detecting the heart rate may include collection of an subcutaneous electrocardiogram (ECG) using an implantable device dedicated to the VNS stimulation alone, the device not including cardiac lead or another mechanism to deliver pulses to the myocardium.
The application of a VNS stimulation delivered, in a period close to synchronism with the R wave of the EGM or ECG (the R wave corresponding to the beginning of the ventricular depolarization), has the effect of inducing a change in the RR interval of the successive cardiac cycles. The RR interval increases with the energy of the stimulation delivered to the vagus nerve, as a high VNS stimulation energy on cardiac function has an inhibitory effect resulting in a rhythm slowdown (measured by RR interval). Conversely, a low VNS stimulation energy has a lesser impact on cardiac function, resulting in a rhythm much closer to the natural sinus rhythm observable in the absence of VNS stimulation.
The evolution of the spontaneous heart rate variability (VSS) is one indicator for assessing the clinical condition of a patient experiencing or at risk of heart failure. A decrease in the VSS indicates a worsening of the heart failure disease. Conversely, an increase in VSS reflects an improvement in the general condition of the patient.
US2007/0233194A1 discloses a VNS electrostimulation device with a pulse generator synchronized to the heart and/or respiratory rate of the patient. The description includes methods for analyzing various cardiac and physiological parameters including heart rate variability (HRV). The sequencing of VNS pulses, in particular the moment for the application of the first pulse of the burst, may be modulated by the generator, randomly or in a predetermined manner. US2009/0088817A1, US2011/0118802A1 and US2013/0131746A1 disclose other examples of VNS stimulators wherein certain characteristics of the stimulation may vary randomly or in a predetermined manner.